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Biomedical subjects

M Zacharias

Publications and source records attributed to M Zacharias.

68 records · Page 4Linked to original sources
PubMed1990

Effects of alfentanil on induction and recovery from propofol anaesthesia in day surgery.

The influence of alfentanil on induction and recovery characteristics of propofol was examined in women presenting as day cases for minor gynaecological surgery. Alfentanil reduced the incidence of pain on injection and the induction and maintenance requirements of propofol. This was at the expense of more prolonged apnoea. Immediate recovery characteristics were similar in each group although changes in Critical Flicker Fusion Threshold as a measure of psychomotor impairment were more pronounced after alfentanil. Such differences were insignificant at three hours by which time Critical Flicker Fusion Threshold had returned to baseline and patients were ready for discharge home.

Adult↗
PubMed1989

Influence of the GCGC discriminator motif introduced into the ribosomal RNA P2- and tac promoter on growth-rate control and stringent sensitivity.

The synthesis of stable RNA in bacteria is known to be regulated by a stringent control mechanism. Characteristic of stringent-regulated promoters, all ribosomal RNA promoters P1, but not P2, contain a GC-rich discriminator sequence assumed to be important for such a control. Using site-directed mutagenesis we have altered both the rrnB P2 and the synthetic tac promoter to the consensus GCGC discriminator motif. The modified promoters were placed upstream of the structural gene encoding the chloramphenicol acetyltransferase. The response of the modified promoters to amino acid starvation, changes in the growth rate or differences in the basal level of guanosine tetraphosphate (ppGpp) were determined in vivo. The results clearly show, that the discriminator motif is sufficient to convert the ribosomal RNA promoter P2 to a stringent, as well as growth-rate regulated, promoter. By contrast, the same discriminator sequence linked to the synthetic tac promoter does not convert this promoter to either stringency or growth-rate regulation. Finally, the results presented in this study reinforce the view that stringent and growth-rate regulation utilize the same mechanism, with ppGpp being the common mediator.

Base Sequence↗
PubMed1989

Functional characterization of a putative internal promoter sequence between the 16S and the 23S RNA genes within the Escherichia coli rrnB operon.

Transcription of ribosomal RNAs in Escherichia coli is started from two strong tandem promoters, P1 and P2. It is known, however, that internal promoter-like structures occur and in a recent report (Mankin et al., 1987) a promoter sequence Pi within the 16S and 23S RNA spacer region showing good homology to the prokaryotic consensus promoter structure was identified. It was proposed that this putative promoter has a possible function in the transcription of ribosomal RNAs in E. coli. Fusion of various DNA fragments containing the putative promoter sequence and different parts of the 16S/23S spacer region as well as the 23S RNA to the galactokinase gene allowed us to assess the functional activity of the promoter in vivo. To determine any growth rate dependent function of the putative promoter, the measurements were performed under different growth conditions. The promoter activity did not exceed 7% of the lac promoter under in vivo assay conditions. In addition, transcription starting at the promoter Pi did not proceed through the entire 23S RNA gene. We conclude, therefore, that transcription from Pi does not contribute significantly to the synthesis of ribosomal RNAs. Thus its functional significance, if any, remains elusive.

DNA, Bacterial↗
PubMed1987

Deletions in the tL structure upstream to the rRNA genes in the E. coli rrnB operon cause transcription polarity.

A number of deletions have been constructed within the leader region of the rrnB operon from E. coli. The deletions remove a potential transcription terminator structure downstream from an antitermination recognition sequence (Box A), which precedes the structural gene for the 16S RNA. Cells harbouring plasmids, where the terminator structure was deleted, partially or totally, showed a reduction in growth rate under minimal growth conditions. Measurement of the ribosomal RNA synthesis rates of such cells determined by pulselabeling and hybridisation to appropriate DNA probes, showed that the amount of the more distally located 23S RNA was reduced compared to the promoter-proximal 16S RNA. This polarity in transcription, resulting in a non-stoichiometric synthesis of the ribosomal RNAs, is most likely the result of a defective antitermination. The reduction in the amount of 23S RNA in such cells is compensated for by an increase in the overall ribosomal RNA synthesis, in concordance with the ribosomal RNA feedback regulation model. The accumulation of transcripts of the tRNAGlu2 gene, coded in the spacer region between the 16S and 23S RNA genes, in cells with an altered rRNA stoichiometry supports this interpretation.

Base Sequence↗
PubMed1987

Comparison of propofol and thiopentone anaesthesia (with special reference to recovery characteristics).

Thiopentone and propofol were used for the induction and maintenance of anaesthesia in unpremedicated patients undergoing minor gynaecological procedures. There were no significant differences in the induction and maintenance characteristics except for a high incidence of pain on injection and a greater fall in the mean systolic blood pressure associated with propofol in comparison with thiopentone. Propofol was associated with a quicker early recovery as well as a faster psychomotor recovery, as tested by a peg-board. However, complete psychomotor recovery was not achieved for up to three hours in some patients receiving propofol and so caution is advised regarding the early street fitness of patients receiving repeated doses of the drug for day case surgery.

Adolescent↗
PubMed1986

The importance of individual nucleotides for the structure and function of rRNA molecules in E. coli. A mutagenesis study.

Methods of in vitro mutagenesis were employed to determine the importance of individual nucleotides within the ribosomal RNAs for the structure and function of E. coli ribosomes. A series of defined nucleotides in the genes for the 5 S and 16 S RNA were altered by transition and transversion mutations using either oligonucleotide-directed or bisulfite-catalyzed mutation procedures. Plasmids harbouring the mutated rRNA genes were expressed and the ribosomes containing such altered RNAs were investigated for impairments in RNA-protein interaction assembly and mRNA-coded tRNA binding.

Base Sequence↗
PubMed1981

Liver enzyme studies with continuous intravenous anaesthesia.

A battery of liver function tests was carried out before operation and on the 3rd--5th and 13th--15th postoperative days in patients anaesthetised with continuous infusion of thiopentone, Althesin or etomidate for an intermediate operation. Some derangement of enzyme activity was found in one quarter to one third of the patients, and was most marked after Althesin. The findings are compared with published data on ketamine, which had an effect on enzyme activities similar to that of Althesin. On pooling data from different studies it became very apparent that large doses of intravenous anaesthetics cause a greater derangement of liver function than that which occurs using a balanced technique for the same operation.

Adult↗
PubMed1979

Effect of preanaesthetic medication on etomidate.

The effects of diazepam and pethidine, when given as preanaesthetic medication, on the induction of anaesthesia and the postanaesthetic sequelae following etomidate were studied in women undergoing minor gynaecological procedures. Pain on injection was present in all the groups. However, the frequency was significantly less with the polyethylene glycol and propylene glycol formulations of the drug compared with the aqueous solution. A fast injection and pethidine premedication decreased the frequency also. The high frequency of excitatory phenomena in unpremedicated patients was decreased significantly by premedication with diazepam and pethidine, especially the latter. Respiratory and cardiovascular effects of the drug were not major problems. The frequency of emetic sequelae was high. Recovery was rapid even in the groups receiving sedative premedication.

Adolescent↗
PubMed1979

Venous sequelae following etomidate.

Five hundred patients receiving one of three different formulations of etomidate were observed on the 2nd and 3rd days after operation for possible venous sequelae. The total frequency of sequelae was 8% or more, the greatest being with the propylene glycol formulation (23%). Formulation of the drug and total dose employed were the most important factors influencing venous sequelae, which were not related to pain on injection.

Adolescent↗
PubMed1978

Evaluation of three preparations of etomidate.

Three formulations of etomidate were evaluated in unpremedicated patients undergoing minor gynaecological procedures. There was a high frequency of pain on injection (up to 50%) and excitatory phenomena (up to 95%) with all formulations. The frequency of excitatory phenomena was significantly greater than that after methohexitone. Recovery was rapid, but emetic sequelae were frequent and significantly more marked than after methohexitone.

Anesthesia, Intravenous↗
PubMedDate not supplied

DAPI binding to the DNA minor groove: a continuum solvent analysis.

A continuum solvent model based on the generalized Born (GB) or finite-difference Poisson-Boltzmann (FDPB) approaches has been employed to compare the binding of 4'-6-diamidine-2-phenyl indole (DAPI) to the minor groove of various DNA sequences. Qualitative agreement between the results of GB and FDPB approaches as well as between calculated and experimentally observed trends regarding the sequence specificity of DAPI binding to B-DNA was obtained. Calculated binding energies were decomposed into various contributions to solvation and DNA-ligand interaction. DNA conformational adaptation was found to make a favorable contribution to the calculated total interaction energy but did not change the DAPI binding affinity ranking of different DNA sequences. The calculations indicate that closed complex formation is mainly driven by nonpolar contributions and was found to be disfavored electrostatically due to a desolvation penalty that outbalances the attractive Coulomb interaction. The calculated penalty was larger for DAPI binding to GC-rich sequences compared with AT-rich target sequences and generally larger for the FDPB vs the GB continuum model. A radial interaction profile for DAPI at different distances from the DNA minor groove revealed an electrostatic energy minimum a few Angstroms farther away from the closed binding geometry. The calculated electrostatic interaction up to this distance is attractive and it may stabilize a nonspecific binding arrangement.

Adenine Nucleotides↗
PubMedDate not supplied

Comparative efficacy and pharmacokinetics of racemic bupivacaine and S-bupivacaine in third molar surgery.

PURPOSE: To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac-bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral impacted third molar extractions. METHOD: A randomised, double blind, two period cross-over design was employed. Six subjects (2 males, 4 females; age 19-25 years; weight 69.2+/-9.4 kg) received bupivacaine hydrochloride injection (6.6 ml) as rac-bupivacaine (0.5% as salt) or S-bupivacaine (0.5% as base) prior to extraction of impacted third molars on one side and three weeks later on the other side. Anesthesia, blood loss associated with surgery and post-operative pain experience were evaluated. Plasma samples were analysed for bupivacaine enantiomers by chiral HPLC. RESULTS: In 7/12 operations, anesthesia adequate for surgery was delayed (>10 min) or unsatisfactory requiring lidocaine rescue medication. Despite this, there were no significant differences in onset and duration of anesthesia, blood loss or post-operative pain experience between the two arms of the study. Pharmacokinetic parameters were not significantly different and there was no evidence of chiral inversion after dosing with S-bupivacaine. CONCLUSIONS: Both study drugs were inadequate as single anesthetic agent for third molar surgery. Any decision to use S-bupivacaine for oral surgery must rest on evidence that it is less toxic than the racemic drug.

Adult↗